RE:News aus der Forschung 2023 - 12

CD133+ endothelial-like stem cells restore neovascularization and promote longevity in progeroid and naturally aged mice

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The stem cell theory of aging dictates that a decline in the number and/or function of stem cells causes tissue degeneration and aging; however, it still lacks unequivocal experimental support. Here, using lineage tracing and single-cell transcriptomics, we identify a population of CD133+ bone marrow-derived endothelial-like cells (ELCs) as potential endothelial progenitor cells, which contribute to tubular structures in vitro and neovascularization in vivo. We demonstrate that supplementation with wild-type and young ELCs respectively restores neovascularization and extends lifespan in progeric and naturally aged mice. Mechanistically, we identify an upregulation of farnesyl diphosphate synthase (FDPS) in aged CD133+ ELCs—a key enzyme in isoprenoid biosynthesis. Overexpression of FDPS compromises the neovascularization capacity of CD133+ ELCs, whereas FDPS inhibition by pamidronate enhances neovascularization, improves health measures and extends lifespan in aged mice. These findings highlight stem cell-based strategies for the treatment of progeria and age-related pathologies.

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https://www.nature.com/articles/s43587-023-00512-z

Common drug may help manage osteoarthritis symptoms and pain

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A recent studyTrusted Source published in The LancetTrusted Source examined how well the drug methotrexate may help treat hand osteoarthritis.

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https://www.medicalnewstoday.com/article...mptoms-and-pain

Food sensitivity may significantly increase risk of cardiovascular disease

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• Researchers are reporting that people with food sensitivities had a significantly higher risk of cardiovascular disease.
• Experts say that changes in the gut microbiome from food sensitivity can affect a person’s cardiovascular system.
• Food allergies are different than food sensitivities. Food allergies affect the immune system and food sensitivities involve the digestive system.

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https://www.medicalnewstoday.com/article...ascular-disease

Zitat von version2 im Beitrag #65

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Dietary neoagarotetraose extends lifespan and impedes brain aging in mice via regulation of microbiota-gut-brain axis
https://www.sciencedirect.com/science/ar...090123223001200

Keine Ahnung was "neoagarotetraose" ist, aber jetzt will ich es auch haben.

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A drug-like molecule engages nuclear hormone receptor DAF-12/FXR to regulate mitophagy and extend lifespan
https://www.nature.com/articles/s43587-023-00524-9

Überrascht oder? Der Mechanismus da hinter ist interessant.

Fluoxetine Promotes Longevity via Reactive Oxygen Species in Caenorhabditis elegans
https://academic.oup.com/biomedgerontolo...ext&login=false

Zitat von Speedy im Beitrag #279

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Überrascht oder? Der Mechanismus da hinter ist interessant.

Fluoxetine Promotes Longevity via Reactive Oxygen Species in Caenorhabditis elegans
https://academic.oup.com/biomedgerontolo...ext&login=false

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Repurposing nucleoside reverse transcriptase inhibitors (NRTIs) to slow aging
https://www.sciencedirect.com/science/ar...VL-KnynQRLU-oTg

Mid-old cells are a potential target for anti-aging interventions in the elderly
https://www.nature.com/articles/s41467-023-43491-w

The rate of epigenetic drift scales with maximum lifespan across mammals

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Epigenetic drift or “disorder” increases across the mouse lifespan and is suggested to underlie epigenetic clock signals. While the role of epigenetic drift in determining maximum lifespan across species has been debated, robust tests of this hypothesis are lacking. Here, we test if epigenetic disorder at various levels of genomic resolution explains maximum lifespan across four mammal species. We show that epigenetic disorder increases with age in all species and at all levels of genomic resolution tested. The rate of disorder accumulation occurs faster in shorter lived species and corresponds to species adjusted maximum lifespan. While the density of cytosine-phosphate-guanine dinucleotides (“CpGs”) is negatively associated with the rate of age-associated disorder accumulation, it does not fully explain differences across species. Our findings support the hypothesis that the rate of epigenetic drift explains maximum lifespan and provide partial support for the hypothesis that CpG density buffers against epigenetic drift.

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https://www.nature.com/articles/s41467-023-43417-6

Kommentar: Können wir die CpG-Dichte erhöhen? Generell liest sich das Abstract für mich erstmal positiv, da die epigenetischen Änderungen also auf einer Zeitskala relativ zur Spezis stattfinden und nicht absolut über Spezies hinweg in gleichem zeitlichen Abstand zustande kommen. Vereinfacht gesagt klingt das, als ließe sich das epigenetische Alter somit leichter beeinflussen.

Hallo,

so einfach ist es leider nicht, denn es gibt verschiedene Mechanismen zur Methylierung/Demethylierung und es handelt sich um lebende Objekte. Die Doppelstrangbrüche sind ein Zeichen für zunehmend versagende Reparaturmechanismen und hier spielt die Deacethylierung evtl. eine Rolle.

Viele Grüße

Roger

#282 @version2
Ich denke wir begehen hier möglicherweise einen Denkfehler. Wie bei Methylierung/Demethylierung haben wir hier vielleicht nur eine verbesserte Altersuhr.

Es ist so ähnlich wie man Ebbe und Flut im Tageswechsel beobachtet und dann denkt, dass die Ebbe z. B. den Sonnenuntergang verursacht. Es sind nur beides Phänomene, die zufällig zeitlich gleichzeitig auftreten.

Jedoch finde ich die Möglichkeit spannend.
Ein Test wäre eben wie bei den Experimenten mit Ratten, wo man Alter induziert hat und dann wieder zurückgängig gemacht hat. Teilweise geht das auch mit Wildtieren.

Das wäre eben der harte Test: Ob man eine in vitro-Kultur (oder eben ein Versuchstier) durch Manipulation künstlich altern und verjüngen kann. Damit wäre der unleugbare Beweis eines kausalen Zusammenhangs erbracht. Wenn z. B. nur altern geht, ist es vielleicht nur eine Art von Streß. Bei nur verjüngen gilt der Einwand des 1. Links.

Zitat von Roger im Beitrag #283

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so einfach ist es leider nicht, denn es gibt verschiedene Mechanismen zur Methylierung/Demethylierung und es handelt sich um lebende Objekte. Die Doppelstrangbrüche sind ein Zeichen für zunehmend versagende Reparaturmechanismen und hier spielt die Deacethylierung evtl. eine Rolle.

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Zitat von Methusalem im Beitrag #284

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Das wäre eben der harte Test: Ob man eine in vitro-Kultur (oder eben ein Versuchstier) durch Manipulation künstlich altern und verjüngen kann. Damit wäre der unleugbare Beweis eines kausalen Zusammenhangs erbracht. Wenn z. B. nur altern geht, ist es vielleicht nur eine Art von Streß. Bei nur verjüngen gilt der Einwand des 1. Links.

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1,5-anhydro-D-fructose induces anti-aging effects on aging-associated brain diseases by increasing 5’-adenosine monophosphate-activated protein kinase activity via the peroxisome proliferator-activated receptor-γ co-activator-1α/brain-derived neurotrophic factor pathway
https://www.aging-us.com/article/205228/text

Erklärender Artikel: https://medicalxpress.com/news/2023-11-a...n-diseases.html

Das aktuelle Paper von David Sinclair und seinem Team.

SIRT2 transgenic over-expression does not impact lifespan in mice
https://onlinelibrary.wiley.com/doi/full/10.1111/acel.14027

Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity
https://www.nature.com/articles/s41586-023-06749-3

The rate of epigenetic drift scales with maximum lifespan across mammals
https://www.nature.com/articles/s41467-023-43417-6

Zitat von Speedy im Beitrag #288

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Trans-vaccenic acid reprograms CD8+ T cells and anti-tumour immunity
https://www.nature.com/articles/s41586-023-06749-3

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Zitat

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Here we use a blood nutrient compound library-based screening approach to demonstrate that dietary trans-vaccenic acid (TVA) directly promotes effector CD8+ T cell function and anti-tumour immunity in vivo. TVA is the predominant form of trans-fatty acids enriched in human milk, but the human body cannot produce TVA endogenously1. Circulating TVA in humans is mainly from ruminant-derived foods including beef, lamb and dairy products such as milk and butter2,3, but only around 19% or 12% of dietary TVA is converted to rumenic acid by humans or mice, respectively4,5. Mechanistically, TVA inactivates the cell-surface receptor GPR43, an immunomodulatory G protein-coupled receptor activated by its short-chain fatty acid ligands6,7,8. TVA thus antagonizes the short-chain fatty acid agonists of GPR43, leading to activation of the cAMP–PKA–CREB axis for enhanced CD8+ T cell function. These findings reveal that diet-derived TVA represents a mechanism for host-extrinsic reprogramming of CD8+ T cells as opposed to the intrahost gut microbiota-derived short-chain fatty acids. TVA thus has translational potential for the treatment of tumours.

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Spannend. Wohl keine guten Nachrichten für Veganer.

Chronological aging impacts abundance, function and microRNA content of extracellular vesicles produced by human epidermal keratinocytes

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The disturbance of intercellular communication is one of the hallmarks of aging. The goal of this study is to clarify the impact of chronological aging on extracellular vesicles (EVs), a key mode of communication in mammalian tissues. We focused on epidermal keratinocytes, the main cells of the outer protective layer of the skin which is strongly impaired in the skin of elderly. EVs were purified from conditioned medium of primary keratinocytes isolated from infant or aged adult skin. A significant increase of the relative number of EVs released from aged keratinocytes was observed whereas their size distribution was not modified. By small RNA sequencing, we described a specific microRNA (miRNA) signature of aged EVs with an increase abundance of miR-30a, a key regulator of barrier function in human epidermis. EVs from aged keratinocytes were found to be able to reduce the proliferation of young keratinocytes, to impact their organogenesis properties in a reconstructed epidermis model and to slow down the early steps of skin wound healing in mice, three features observed in aged epidermis. This work reveals that intercellular communication mediated by EVs is modulated during aging process in keratinocytes and might be involved in the functional defects observed in aged skin.

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https://www.aging-us.com/article/205245/text

Kommentar: Diese EVs scheinen durchaus eine Rolle bei der Alterung zu spielen. Ob eine epigenetische Verjüngung auch die EVs verjüngen würde?

"Cohort profile: Genetic data in the German Socio-Economic Panel Innovation Sample (SOEP-G)"
> https://journals.plos.org/plosone/articl...al.pone.0294896

Interessante Daten zum Thema Genetik.

LEF1 isoforms regulate cellular senescence and aging
https://onlinelibrary.wiley.com/doi/full...gn=wolearlyview

Extending healthspans by targeting the hallmarks of aging

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Diseases associated with aging have a profound impact on the quality of life. Hearing and vision loss, frailty and dementia are some of the common conditions affecting older individuals. With the number of people aged over 65 set to more than double by 2050, there is an urgent need to extend the healthy lifespan.
Since its inception in 2019, Rejuveron has invested in six portfolio companies—two of which are in the clinic—to address some of the hallmarks of aging, such as stem cell exhaustion, telomere shortening, and cellular senescence (Fig. 1).

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https://www.nature.com/articles/d43747-023-00122-z

Efficient elimination of MELAS-associated m.3243G mutant mitochondrial DNA by an engineered mitoARCUS nuclease
https://www.nature.com/articles/s42255-023-00932-6

IGF2 deficiency promotes liver aging through mitochondrial dysfunction and upregulated CEBPB signaling in d-galactose-induced aging mice
https://molmed.biomedcentral.com/article...020-023-00752-0

Transplanting old organs promotes senescence in young recipients
https://www.amjtransplant.org/article/S1...0803-1/fulltext

Kommentar: Studie an Mäusen.

Beunruhigend:
"These observations went along with compromised physical performance and impaired spatial learning and memory abilities."

Allerdings müsste man den Effekt theoretisch auch in vitro nachstellen können.

Es fragt sich, was passieren würde, wenn man geklonte und künstlich verjüngte Organe transplantieren würde?

Zitat von Methusalem im Beitrag #296

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Es fragt sich, was passieren würde, wenn man geklonte und künstlich verjüngte Organe transplantieren würde?

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Unlocking the secrets of aging: Epigenetic reader BRD4 as the target to combatting aging-related diseases
https://www.sciencedirect.com/science/ar...QvKiJ_mJiRrehAI

"Are your organs ageing well? The blood holds clues"

Zitat draus:
"Around one-fifth of the more than 5,600 people who participated in the study met the authors’ criteria for accelerated ageing for at least one organ. Such hyper-aged organs are linked to a higher prevalence of disease, and having one organ of unusually advanced age is linked to a higher risk of premature death, the study found."

Siehe auch:
t544f10-News-aus-der-Forschung-11.html#msg58831#msg58831

Es scheint, dass wir nicht in allen Bereichen gleichschnell altern.

Zitat von version2 im Beitrag #280

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Zitat von Speedy im Beitrag #279

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Überrascht oder? Der Mechanismus da hinter ist interessant.

Fluoxetine Promotes Longevity via Reactive Oxygen Species in Caenorhabditis elegans
https://academic.oup.com/biomedgerontolo...ext&login=false

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Demnach wären Antioxidantien im Rundwurm ggf. lebensverkürzend? Wäre schon blöd. Vielleicht gibt es da noch andere Effekte die sich nicht im Abstract finden oder die nicht bemerkt wurden.

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